Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes.

Adult Age Factors Aged Datasets as Topic Female Genetic Loci Genome-Wide Association Study Humans Male Middle Aged Polymorphism, Single Nucleotide Polysomnography Self Report / statistics & numerical data Sex Factors Sleep / genetics Sleepiness Young Adult

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
13 08 2019
Historique:
received: 26 11 2018
accepted: 27 06 2019
entrez: 15 8 2019
pubmed: 15 8 2019
medline: 18 12 2019
Statut: epublish

Résumé

Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.

Identifiants

DOI: 10.1038/s41467-019-11456-7 PMID: 31409809 PMC: PMC6692391
pubmed: 31409809
doi: 10.1038/s41467-019-11456-7
pii: 10.1038/s41467-019-11456-7
pmc: PMC6692391
doi:

Types de publication

Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3503

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : R01 HG003054
Pays : United States
Organisme : Medical Research Council
ID : MR/P023576/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL113338
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135824
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127564
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135818
Pays : United States
Organisme : Wellcome Trust
ID : 107851/Z/15/Z
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK102696
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK102323
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00011/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P023576/2
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : T32 HL007567
Pays : United States
Organisme : Medical Research Council
ID : MR/M008908/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P012167/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : K01 HL136884
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107859
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL135405
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK105072
Pays : United States

Références

Cell Metab. 2009 Nov;10(5):366-78
pubmed: 19883615
Trends Neurosci. 2012 Dec;35(12):723-32
pubmed: 22858523
Elife. 2018 May 30;7:
pubmed: 29846171
Cell. 1999 Aug 6;98(3):365-76
pubmed: 10458611
Eur J Neurosci. 2010 Feb;31(3):499-507
pubmed: 20105243
Nat Genet. 2015 Nov;47(11):1228-35
pubmed: 26414678
PLoS One. 2017 Feb 1;12(2):e0169649
pubmed: 28146576
PLoS Comput Biol. 2016 Jan 25;12(1):e1004714
pubmed: 26808494
J Thorac Dis. 2012 Dec;4(6):608-16
pubmed: 23205286
Sleep Med. 2014 Jul;15(7):782-8
pubmed: 24841111
Lancet Respir Med. 2015 Oct;3(10):769-81
pubmed: 26423011
Int J Epidemiol. 2013 Aug;42(4):968-77
pubmed: 22879362
Nat Commun. 2019 Mar 7;10(1):1100
pubmed: 30846698
Nat Genet. 2015 Mar;47(3):284-90
pubmed: 25642633
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Nat Genet. 2017 Feb;49(2):274-281
pubmed: 27992416
Am J Med Genet B Neuropsychiatr Genet. 2013 Jul;162B(5):439-51
pubmed: 23728906
Biol Psychiatry. 1996 Mar 15;39(6):411-8
pubmed: 8679786
Sci Transl Med. 2010 Jan 13;2(14):14ra3
pubmed: 20371466
Sci Rep. 2018 Aug 28;8(1):12975
pubmed: 30154500
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Nat Genet. 2012 Mar 18;44(4):369-75, S1-3
pubmed: 22426310
Twin Res. 2004 Dec;7(6):589-95
pubmed: 15607009
Nat Genet. 2019 Mar;51(3):387-393
pubmed: 30804566
J Clin Endocrinol Metab. 2005 Aug;90(8):4510-5
pubmed: 15941867
Sleep. 2005 Apr;28(4):479-96
pubmed: 16171293
Nat Genet. 2016 Jul;48(7):709-17
pubmed: 27182965
Respir Med. 2000 Oct;94(10):971-6
pubmed: 11059950
Sleep Med Rev. 2008 Apr;12(2):129-41
pubmed: 18342261
Sleep. 2015 Mar 01;38(3):351-60
pubmed: 25581913
Sleep. 2004 May 1;27(3):423-33
pubmed: 15164894
Nature. 2011 Oct 12;478(7370):476-82
pubmed: 21993624
J Clin Sleep Med. 2006 Apr 15;2(2):S7-11
pubmed: 17557501
Curr Biol. 2012 Jun 19;22(12):1142-8
pubmed: 22658601
BMC Med Genet. 2007 Sep 19;8 Suppl 1:S9
pubmed: 17903308
Sleep. 2001 Jun 15;24(4):392-400
pubmed: 11403523
PLoS One. 2015 Nov 16;10(11):e0142533
pubmed: 26569414
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Sleep. 2006 May;29(5):645-9
pubmed: 16774154
Sleep Med. 2012 Sep;13(8):985-90
pubmed: 22704400
Int J Epidemiol. 2018 Aug 1;47(4):1264-1278
pubmed: 29961852
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
Bioinformatics. 2017 Jan 15;33(2):272-279
pubmed: 27663502
PeerJ. 2013 Apr 16;1:e66
pubmed: 23646285
Int J Epidemiol. 2018 Jun 1;47(3):696-696i
pubmed: 29165699
Rev Neurosci. 2014;25(3):429-37
pubmed: 24681431
Nature. 2015 Feb 19;518(7539):337-43
pubmed: 25363779
Arch Intern Med. 2002 Jan 28;162(2):201-8
pubmed: 11802754
Int J Epidemiol. 2016 Dec 1;45(6):1961-1974
pubmed: 27616674
Am J Hum Genet. 2015 Dec 3;97(6):894-903
pubmed: 26637979
Nat Commun. 2016 Feb 02;7:10448
pubmed: 26835600
J Sleep Res. 2001 Mar;10(1):53-8
pubmed: 11285055
J Appl Physiol (1985). 2014 Oct 1;117(7):738-44
pubmed: 25103964
Brain Res Bull. 2010 Sep 30;83(3-4):93-102
pubmed: 20433910
Nat Commun. 2019 Jan 29;10(1):343
pubmed: 30696823
Int J Epidemiol. 2011 Dec;40(6):1431-7
pubmed: 22158659
Curr Opin Lipidol. 2015 Apr;26(2):88-95
pubmed: 25692341
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
Sleep Med. 2018 Jul;47:106-112
pubmed: 29783161
Am J Respir Cell Mol Biol. 2018 Mar;58(3):391-401
pubmed: 29077507
Mol Psychiatry. 2015 May;20(5):647-656
pubmed: 25288136
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Nature. 2018 Oct;562(7726):210-216
pubmed: 30305740
Cell. 2013 Nov 7;155(4):765-77
pubmed: 24209692
Neuron. 2017 Feb 22;93(4):747-765
pubmed: 28231463
Nat Commun. 2019 Apr 5;10(1):1585
pubmed: 30952852
PLoS Med. 2018 Sep 21;15(9):e1002654
pubmed: 30240442
Lancet Neurol. 2017 Nov;16(11):898-907
pubmed: 29029846
Prog Neurobiol. 2012 Oct;99(1):1-14
pubmed: 22705413

Auteurs

Heming Wang (H)

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
ORCID: 0000-0002-1486-7495

Jacqueline M Lane (JM)

Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Samuel E Jones (SE)

Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.
ORCID: 0000-0003-0153-922X

Hassan S Dashti (HS)

Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-1650-679X

Hanna M Ollila (HM)

Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA.
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.

Andrew R Wood (AR)

Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.

Vincent T van Hees (VT)

Netherlands eScience Center, Amsterdam, Netherlands.
ORCID: 0000-0003-0182-9008

Ben Brumpton (B)

K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Department of Thoracic and Occupational Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
ORCID: 0000-0002-3058-1059

Bendik S Winsvold (BS)

K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
Division of Clinical Neuroscience, Oslo University Hospital and University of Oslo, Oslo, Norway.
ORCID: 0000-0003-4171-8919

Katri Kantojärvi (K)

Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
Department of Psychiatry and SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Teemu Palviainen (T)

Institute for Molecular Medicine FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
ORCID: 0000-0002-7847-8384

Brian E Cade (BE)

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.

Tamar Sofer (T)

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
ORCID: 0000-0001-8520-8860

Yanwei Song (Y)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Northeastern University College of Science, Boston, MA, USA.
ORCID: 0000-0002-2411-6548

Krunal Patel (K)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Northeastern University College of Science, Boston, MA, USA.

Simon G Anderson (SG)

Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
The George Alleyne Chronic Disease Research Centre, Caribbean Institute for Health Research, University of the West Indies, Cave Hill, Barbados.
ORCID: 0000-0002-8896-073X

David A Bechtold (DA)

Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
ORCID: 0000-0001-8676-8704

Jack Bowden (J)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Richard Emsley (R)

Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

Simon D Kyle (SD)

Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Max A Little (MA)

Department of Mathematics, Aston University, Birmingham, UK.
Media Lab, Massachusetts Institute of Technology, Cambridge, MA, USA.

Andrew S Loudon (AS)

Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

Frank A J L Scheer (FAJL)

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
ORCID: 0000-0002-2014-7582

Shaun M Purcell (SM)

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.

Rebecca C Richmond (RC)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
School of Social and Community Medicine, University of Bristol, Bristol, UK.
ORCID: 0000-0003-0574-5071

Kai Spiegelhalder (K)

Clinic for Psychiatry and Psychotherapy, Medical Centre, University of Freiburg, Freiburg, Germany.

Jessica Tyrrell (J)

Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.
ORCID: 0000-0002-9256-6065

Xiaofeng Zhu (X)

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.

Christer Hublin (C)

Institute for Molecular Medicine FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Department of Public Health, University of Helsinki, Helsinki, Finland.

Jaakko A Kaprio (JA)

Institute for Molecular Medicine FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.
Department of Public Health, University of Helsinki, Helsinki, Finland.
ORCID: 0000-0002-3716-2455

Kati Kristiansson (K)

Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
ORCID: 0000-0003-4688-107X

Sonja Sulkava (S)

Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
Department of Psychiatry and SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Tiina Paunio (T)

Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
Department of Psychiatry and SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Kristian Hveem (K)

K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.

Jonas B Nielsen (JB)

Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.

Cristen J Willer (CJ)

Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.
ORCID: 0000-0001-5645-4966

John-Anker Zwart (JA)

Division of Clinical Neuroscience, Oslo University Hospital and University of Oslo, Oslo, Norway.

Linn B Strand (LB)

K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.

Timothy M Frayling (TM)

Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.

David Ray (D)

NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, OX39DU, UK.

Deborah A Lawlor (DA)

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
ORCID: 0000-0002-6793-2262

Martin K Rutter (MK)

Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Manchester Diabetes Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Michael N Weedon (MN)

Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom.

Susan Redline (S)

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Department of Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Richa Saxena (R)

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. rsaxena@partners.org.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. rsaxena@partners.org.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. rsaxena@partners.org.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. rsaxena@partners.org.
ORCID: 0000-0003-2233-1065

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Genome-wide association analysis of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Facteurs épidémiologiques › Facteurs âges › Genome-wide association analysis of...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Genome-wide association analysis of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Jeux de données comme sujet › Genome-wide association analysis of...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Genome-wide association analysis of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genome-wide association analysis of...
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questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Sommeil › Genome-wide association analysis of...
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